Role of oxidative stress and inflammation-related signaling pathways in doxorubicin-induced cardiomyopathy

Doxorubicin (DOX) is a powerful and commonly used chemotherapeutic drug, used alone or in combination in a variety of cancers, while it has been found to cause serious cardiac side effects in clinical application. More and more researchers are trying to explore the molecular mechanisms of DOX-induced cardiomyopathy (DIC), in which oxidative stress and inflammation are considered to play a significant role. This review summarizes signaling pathways related to oxidative stress and inflammation in DIC and compounds that exert cardioprotective effects by acting on relevant signaling pathways, including the role of Nrf2/Keap1/ARE, Sirt1/p66Shc, Sirt1/PPAR/PGC-1 alpha signaling pathways and NOS, NOX, Fe2+ signaling in oxidative stress, as well as the role of NLRP3/caspase-1/GSDMD, HMGB1/TLR4/MAPKs/NF-kappa B, mTOR/TFEB/NF-kappa B pathways in DOX-induced inflammation. Hence, we attempt to explain the mechanisms of DIC in terms of oxidative stress and inflammation, and to provide a theoretical basis or new idea for further drug research on reducing DIC.

Automated summary

Doxorubicin is a powerful chemotherapeutic drug used in cancer treatment, but it can cause serious cardiac side effects. Researchers are exploring the molecular mechanisms of doxorubicin-induced cardiomyopathy, focusing on oxidative stress and inflammation.